The role of radiation therapy in the treatment of metastatic cancer

Radiation therapy continues to play an important role in the management of cancer. In this review, we discuss the use of radiation therapy to target and control micrometastatic disease (adjuvant use of radiation), or using stereotactic radiation therapy to address small volumes of gross disease, such as oligometastases, and finally the use of radiation therapy in the era of immunotherapy. Radiation therapy is commonly used to treat nodal basins suspected of harboring microscopic disease. More recently, computer and technical innovations have allowed radiation oncologists to treat small volumes of gross disease within the brain and also in the body with great success, adding to the cancer armamentarium. This modality of cancer treatment that began shortly after the discovery of X-rays by William Roentgen continues to evolve and finds new clinical applications which minimize toxicity while increasing effectiveness. The newly discovered interactions of high dose/fraction radiation (stereotactic radiosurgery) with immune check point inhibitors in melanoma is the latest example of how synergism can be achieved between two different modalities thus increasing the therapeutic ratio to control metastatic cancer.     

The interactions of vanadium with Phycomyces blakesleeanus mycelium: enzymatic reduction,transport and metabolic effects

The biological and chemical basis of vanadium action and transport in fungi is relatively poorly understood. In this study we investigated the interactions of vanadium in physiologically-relevant redox states: vanadate (+5) and vanadyl (+4), with mycelium of fungus Phycomyces blakesleeanus using EPR and ³¹P NMR spectroscopy and biochemical assays. We determined that P. blakesleeanus reduces V⁵⁺ to V⁴⁺ in the extracellular compartment by the means of cell surface enzyme with ferricyanide reductase activity, which contains molybdenum–molybdopterin as a cofactor. Both, V⁵⁺ and V⁴⁺ bind to cell wall. They enter the cytoplasm via phosphate transporter and cation channels, respectively, and exhibit different metabolic effects. Vanadate provokes increased biomass production, the effects being inverted to toxic at higher V⁵⁺ concentrations. In addition, V⁵⁺ activates the synthesis of sugar phosphates and oligophosphates. On the other hand, V⁴⁺ exhibits toxic effects even at low concentrations. The V⁴⁺ detoxification route involves binding to vacuolar polyphosphates. Altogether our results imply that the mechanism of interaction of vanadium with P. blakesleeanus involves three major steps: extracellular enzymatic V⁵⁺/V⁴⁺ reduction, V⁴⁺ influx, and vacuolar storage, with an additional step – V⁵⁺ import occurring at higher vanadate concentrations.     

Fusarium: two endophytic novel species from tropical grasses of northern Australia

Two new species of Fusarium associated with Australian indigenous grasses in natural ecosystems are described as F. lyarnte and F. werrikimbe on the basis of morphology, DNA fingerprinting and phylogenetic analysis of EF-1α and β-tubulin sequence data. Isolates of these species were initially recovered from soil in the McGraths Creek area of central Australia and subsequently recovered from soil and stems of the indigenous grass Sorghum interjectum from Litchfield National Park in the Northern Territory, and from Sorghum leiocladum from Werrikimbe National Park in New South Wales. The common feature of both of these species is the production of large globose microconidia in false heads on polyphialides. Attempts to apply the biological species concept were unsuccessful.     

Modeling the relationship between Higuchi’s fractal dimension and Fourier spectra of physiological signals

The exact mathematical relationship between FFT spectrum and fractal dimension (FD) of an experimentally recorded signal is not known. In this work, we tried to calculate signal FD directly from its Fourier amplitudes. First, dependence of Higuchi's FD of mathematical sinusoids on their individual frequencies was modeled with a two-parameter exponential function. Next, FD of a finite sum of sinusoids was found to be a weighted average of their FDs, weighting factors being their Fourier amplitudes raised to a fractal degree. Exponent dependence on frequency was modeled with exponential, power and logarithmic functions. A set of 280 EEG signals and Weierstrass functions were analyzed. Cross-validation was done within EEG signals and between them and Weierstrass functions. Exponential dependence of fractal exponents on frequency was found to be the most accurate. In this work, signal FD was for the first time expressed as a fractal weighted average of FD values of its Fourier components, also allowing researchers to perform direct estimation of signal fractal dimension from its FFT spectrum.     

MicroRNA-148b Targets the TGF-β Pathway to Regulate Angiogenesis and Endothelial-to-Mesenchymal Transition during Skin Wound Healing

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Genetic alterations in quadruple malignancies of a patient with multiple sclerosis: their role in malignancy development and response to therapy

Multiple cancers represent 2.42% of all human cancers and are mainly double or triple cancers. Many possible causes of multiple malignancies have been reported such as genetic alterations, exposure to anti-cancer chemotherapy, radiotherapy, immunosuppressive therapy and reduced immunologic response. We report a female patient with multiple sclerosis and quadruple cancers of different embryological origin. Patient was diagnosed with stage III (T3, N1a, MO) medullary thyroid carcinoma (MTC), multicentric micropapillary thyroid carcinoma, scapular and lumbar melanomas (Clark II, Breslow II), and lobular invasive breast carcinoma (T1a, NO, MO). All tumors present in our patient except micropapillary thyroid carcinomas were investigated for gene alterations known to have a key role in cancer promotion and progression. Tumor samples were screened for the p16 alterations (loss of heterozygosity and homozygous deletions), loss of heterozygosity of PTEN, p53 alterations (mutational status and loss of heterozygosity) and mutational status of RET, HRAS and KRAS. Each type of tumor investigated had specific pattern of analyzed genetic alterations. The most prominent genetic changes were mutual alterations in PTEN and p53 tumor suppressors present in breast cancer and two melanomas. These co-alterations could be crucial for promoting development of multiple malignancies. Moreover the insertion in 4^th codon of HRAS gene was common for all tumor types investigated. It represents frameshift mutation introducing stop codon at position 5 which prevents synthesis of a full-length protein. Since the inactivated RAS enhances sensitivity to tamoxifen and radiotherapy this genetic alteration could be considered as a good prognostic factor for this patient.     

Pesticides Residues and Metals in Plant Products from Agricultural Area of Belgrade,Serbia

The objective of study was to assess the levels of selected metals and pesticides in plant products from agricultural area of Belgrade, Serbia in order to indicate their possible sources and risks of contamination and to evaluate their sanitary probity and safety. The concentrations of cadmium, copper, iron, manganese, nickel, lead and zinc were below limits established by national and international regulations (maximum found concentrations were 0.028, 1.91, 11.16, 1.77, 0.605, 0.073 and 1.76 mg kg⁻¹ respectively). Only residue of one of examined pesticides was found in amount below MRL (bifenthrin 2.46 μg kg⁻¹) in only one of analysed samples, while others were below detection limits. Obtained results indicate that crops from examined agricultural areas are unpolluted by contaminants used for plant protection and nutrition, indicating good agricultural practice regarding pesticides and fertilizer usage as well as moderate industrial production within examined areas.